Acute pancreatitis following paracetamol overdose

Abstract

A 17-year-old woman presented with acute abdominal pain and vomiting 3 h after she attempted to commit suicide by ingesting 30×500 mg paracetamol tablets. The woman was found to have a raised amylase level, and a CT scan confirmed the diagnosis of acute pancreatitis. According to the Naranjo adverse drug reaction probability scale, it is likely that the pancreatitis was induced by the paracetamol ingestion. A literature search reported 36 cases of pancreatitis following excessive doses of paracetamol, however this possible drug reaction is not widely recognised and not documented in the British National Formulary (BNF) list of possible adverse reactions from paracetamol. Being aware of the possibility that abdominal pain following paracetamol overdose may be a manifestation of pancreatitis can help the early detection and initiation of treatment for pancreatitis.

Background

Deliberate self-harm in the form of paracetamol overdose is extremely common. As well as treating the hepatotoxicity and renal dysfunction effects of the drug, one should be aware that a rare complication of the overdose could be pancreatitis. The abdominal pain from the pancreatitis may be falsely attributed to possible liver or gastric causes. More studies are required to investigate the possible association and the mechanism of pancreatic injury.

Case presentation

A 17-year-old Caucasian woman presented with severe epigastric pain and vomiting 3 h after she had ingested 30×500 mg paracetamol tablets with water. She had no other medical comorbidities and denied taking any regular medication. In the days leading to the overdose, her close friend had died suddenly. She did not smoke, drink alcohol or participate in any recreational drug use including at the time of the overdose.

Investigations

Physical examination was remarkable for epigastric tenderness with guarding. Laboratory studies on admission revealed white cell count of 17.7×10⁹/litre, neutrophils 15.24×10⁹/litre, amylase 529 U/litre. Urea, electrolytes, γ-glutamyl transpeptidase, calcium and liver function tests were normal. Paracetamol levels were below the treatment line.

An ultrasound did not reveal any calculi within the gallbladder nor biliary dilatation. A CT scan (fig 1) demonstrated acute pancreatitis with free fluid collection between the pancreatic tail and body of the stomach.

Figure 1.

CT scan: acute pancreatitis with free fluid collection between the pancreatic tail and body of the stomach.

Differential diagnosis

Other possible causes of pancreatitis were investigated. The ultrasound excluded gallstones. The patient denied having taken any other drugs, alcohol or any other substances and the toxicology screen was negative. γ-Glutamyl transpeptidase was also not elevated.

The lipid profile did not show any evidence of hyperlipidaemia. Rubella serology was normal, anti-nuclear antibody and anti-neutrophil cytoplasmic antibody were both negative. There was no history of trauma or foreign travel. The family history was unremarkable and there was nothing to suggest any evidence for cystic fibrosis.

A significant proportion of pancreatitis is idiopathic, and it cannot be excluded that this may have been the true cause of the pancreatitis with the timing of the overdose being coincidental.

Outcome and follow-up

The patient made a good clinical recovery. During her hospital stay her maximum Imrie score was 1 (lactate dehydrogenase >600 U/litre). Her management essentially included adequate analgesia, intravenous fluids and adherence to a low fat diet. Her case was reviewed by the psychiatric team and appropriate follow-up was arranged as an outpatient.

There was no derangement of her hepatic or renal function.

Discussion

The diagnosis of acute pancreatitis was made based on clinical findings in combination with blood test results and confirmed by CT scan. The association between paracetamol overdose and pancreatitis was first published in 1977.¹ Since then, two other case reports have been published which have implicated paracetamol in the development of acute pancreatitis.^2,3

Another study conducted in Denmark investigated 602 patients admitted with paracetamol overdose.⁴ The study found 33 cases of paracetamol-associated acute pancreatitis. Paracetamol is not currently listed among the drugs associated with pancreatitis. This could represent its rarity, but could also be a reflection of the difficulty in making a diagnosis given the presenting history and symptoms.

Appropriate treatment of such cases includes the management of the hepatotoxic and renal dysfunction effects of the condition in conjunction with the treatment of pancreatitis.

It is important to exclude other more common causes of pancreatitis such as cholelithiasis, alcohol consumption, hypercalcaemia and hyperlipidaemia.

The assessment of the probability of an adverse drug reaction is problematic. The Naranjo adverse drug reaction probability scale (table 1) is commonly used in clinical practice.⁵ Implementation of this probability scale yielded a score of 5, which correlates to a probable adverse drug reaction association. There were some elements of the scoring system that could not be assessed due to ethical reasons (eg, did the adverse reaction reappear when the drug was readministered?).

Table 1.

The Naranjo adverse drug reaction probability scale

	Yes	No	Don’t know	Score
1. Are there previous conclusive reports on this reaction?	+1	0	0	1
2. Did the adverse event occur after the suspected drug was administered?	+2	−1	0	2
3. Did the adverse reaction improve when the drug was discontinued or a specific antagonist was administered?	+1	0	0	0
4. Did the adverse reaction reappear when the drug was readministered?	+2	−1	0	0
5. Are there alternative causes (other than the drug) that could have on their own caused the reaction?	−1	+2	0	0
6. Did the reaction reappear when a placebo was given?	−1	+1	0	0
7. Was the drug detected in the blood (or other fluids) in concentrations known to be toxic?	+1	0	0	1
8. Was the reaction more severe when the dose was increased or less severe when the dose was decreased?	+1	0	0	0
9. Did the patient have a similar reaction to the same or similar drugs in any previous exposure?	+1	0	0	0
10. Was the adverse event confirmed by any objective evidence?	+1	0	0	1
Total				5

Table shows Naranjo adverse reaction probability scale scores in this case of acute pancreatitis following paracetamol overdose.

The mechanism by which paracetamol may induce acute pancreatitis is unknown and further studies are required to investigate this.

Learning points

• It is possible that acute pancreatitis may be a complication of paracetamol overdose.

• Clinicians should be aware that patients that present with abdominal pain following paracetamol overdose should have an amylase level requested in addition to other blood tests (liver function tests, urea and electrolytes, paracetamol levels and so on).

• The treatment of pancreatitis is essentially supportive, however in cases where it follows paracetamol overdose N-acetylcysteine may be beneficial assuming paracetamol levels are appropriately above the treatment line.

• Other more common causes of pancreatitis should be investigated before an assumption is made that the condition was induced by paracetamol overdose.